Hormesis as a mechanism for the anti-aging effects of calorie restriction

Abstract

Hormesis in aging is represented by stress-induced stimulation of protective mechanisms and strengthened homeostasis/homeodynamics. Since calorie restriction (CR) generally stimulates various maintenance and repair systems, hormesis has been considered as one of the possible mechanisms. The evidence in favour of the hormetic explanation for the beneficial effects of CR includes the induction of various stress responses including heat shock response, unfolded protein response, autophagy, DNA repair response, sirtuin response, and antioxidant responses. In addition, chronically increased levels of corticosterones and an accompanying decrease in body weight in CR animals is indicative of CR being a stressor and a hormetic agent. Although the exact nature of the low level damage-inducing aspect of CR is yet to be elucidated, a metabolic shift from glycolytic pathways to mitochondrial pathways, which results in enhanced oxidative stress and increased damage to macromolecules and organelles, appears to be the initiator of stress-induced hormetic effects of CR. Periodic modulation of dietary input as a hormetic intervention may be applicable to human beings for slowing down aging.